Effects of Gancao Nourish-Yin Decoction on Liver Metabolic Profiles in hTNF-α Transgenic Arthritic Model Mice

Abstract

Objective Gancao Nourish-Yin Decoction (GNYD) has been applied to clinical rheumatoid arthritis (RA) patients, and it had shown effectiveness not only in disease activity controlling but also in improving patients' physical status. However, its mechanism of function has not been investigated. Metabolic perturbations have been associated with RA, and targeting the metabolic profile is one of the ways to manage the disease. The aim of this study is to observe the effect of GNYD on metabolic changes of human tumor necrosis factor α (hTNF-α) transgenic arthritic model mice. Methods hTNF-α transgenic arthritic model mice were divided into the control group and the GNYD group with six mice in each group. After 8 weeks of treatment, liver tissues of mice in both groups were obtained for liquid chromatography-mass spectrometry analysis. Significantly regulated metabolites by GNYD treatment were first identified, followed by Kyoto Encyclopedia of Genes and Genomes pathway and network analysis. Results A total of 126 metabolites were detected in the liver. Compared with the control group, 17 metabolites in the GNYD group were significantly altered. Specifically, thiamine, gamma-L-glutamyl-L-valine, pantothenic acid, pyridoxal (vitamin B6), succinic acid, uridine 5′-diphospho-glucuronic acid, uridine, allantoic acid, N-acetyl-D-glucosamine, nicotinamide ribotide, and N2, N2-dimethylguanosine were down-regulated by GNYD treatment, whereas isobutyrylglycine, N-acetylcadaverine, N-carbamoyl-L-aspartic acid, L-anserine, creatinine, and cis-4-hydroxy-D-proline were up-regulated. Six metabolic pathways were significantly altered including the alanine, aspartate, and glutamate metabolism; pyrimidine metabolism; thiamine metabolism; amino sugar and nucleotide sugar metabolism; pantothenate and CoA biosynthesis; and citrate cycle. Integrative metabolic network analysis suggested the possibility of GNYD having both positive and negative effects on RA through the suppression of angiogenesis and the promotion of leukocyte extravasation into the synovium, respectively. Conclusions GNYD can modulate the hepatic metabolism of hTNF-α transgenic arthritic model mice. Further optimization of this decoction may lead to better therapeutic effects on RA patients.